JP7019433B2 - エアロゾルの調製のための方法及び組成物 - Google Patents
エアロゾルの調製のための方法及び組成物 Download PDFInfo
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- JP7019433B2 JP7019433B2 JP2018010149A JP2018010149A JP7019433B2 JP 7019433 B2 JP7019433 B2 JP 7019433B2 JP 2018010149 A JP2018010149 A JP 2018010149A JP 2018010149 A JP2018010149 A JP 2018010149A JP 7019433 B2 JP7019433 B2 JP 7019433B2
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Description
10μm超の粒子については、容器1つ当たり6000個を超えない
25μm超の粒子については、容器1つ当たり600個を超えない
該組成物が0.001%(v:v)~1%(v:v)の濃度で界面活性剤を更に含み、
該1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが、該組成物中に20mg/mL以上の濃度で存在し、かつ/又は
該組成物を振動メッシュネブライザーにおいて噴霧化する、免疫グロブリン単一可変ドメインのエアロゾルを調製する方法に関する。
該組成物が0.001%(v:v)~1%(v:v)の濃度で界面活性剤を更に含み、
該1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが、該組成物中に20mg/mL以上の濃度で存在し、かつ/又は
該組成物を振動メッシュネブライザーにおいて噴霧化する、免疫グロブリン単一可変ドメインのエアロゾルを調製する方法に関する。
本発明のポリペプチドの7%未満(より好ましくは6%未満、5%未満、更により好ましくは4%未満、3%未満、2%未満、又は最も好ましくは1%未満)が凝集体(本明細書中で定義される)を形成し、
本発明のポリペプチドの少なくとも80%(少なくとも85%、少なくとも90%、少なくとも95%、少なくとも98%、少なくとも99%又は少なくとも99.5%)が、その標的の少なくとも1つ(好ましくは全て)に対するその結合活性(例えばELISA及び/又はBiacoreによって評価される)を保持する。
a)宿主又は宿主細胞を上記宿主又は宿主細胞が増殖するような条件下で培養する工程と、
b)上記宿主又は宿主細胞を、上記宿主又は宿主細胞がポリペプチドを発現及び/又は産生するような条件下で維持する工程と、
c)分泌されたポリペプチドを培地から単離及び/又は精製する工程とを少なくとも含む。
1.凝集体形成の量が6%以下である(凝集体形成の%はSE-HPLCによって求められるようなものである)、免疫グロブリン単一可変ドメインのエアロゾルを調製する方法であって、水性担体と、1mg/mL~200mg/mLの濃度で、1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドとを含む組成物を噴霧化する工程を含み、
該組成物が0.001%~1%の濃度で界面活性剤を更に含み、
該1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが、該組成物中に20mg/mL以上の濃度で存在し、かつ/又は
該組成物を振動メッシュネブライザーにおいて噴霧化する、免疫グロブリン単一可変ドメインのエアロゾルを調製する方法。
2.凝集体形成の量が5%以下、好ましくは4%以下、例えば3%以下、2%以下又は更には1%以下である、態様1に記載の方法。
3.組成物が、0.001%~1%、好ましくは0.001%~約0.1%、又は約0.01%~約0.1%、例えば約0.001%、0.005%、0.01%、0.02%、0.05%、0.08%若しくは0.1%、好ましくは約0.01%の濃度で界面活性剤を更に含む、態様1又は2に記載の方法。
4.界面活性剤が非イオン性洗剤から選択される、態様1~3のいずれかに記載の方法。
5.界面活性剤がポリソルベート(例えばTween 20及びTween 80)及びポロキサマーから選択されるか、又はPEGを界面活性剤様化合物として添加する、態様1~4のいずれかに記載の方法。
6.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL未満の濃度で存在する、態様3~5のいずれかに記載の方法。
7.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL以上の濃度で存在する、態様1~5のいずれかに記載の方法。
8.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL以上の濃度で存在し、かつ該組成物が界面活性剤を含まない、態様1又は2に記載の方法。
9.ポリペプチドが1つの免疫グロブリン単一可変ドメインを含む、態様1~8のいずれかに記載の方法。
10.ポリペプチドが2つ以上、例えば2つ又は3つの免疫グロブリン単一可変ドメインを含む、態様1~8のいずれかに記載の方法。
11.ポリペプチドがRSV又はIL-23に特異的に結合する、態様1~10のいずれかに記載の方法。
12.ポリペプチドが配列番号1、配列番号2及び配列番号3のうちの1つから選択される態様11に記載の方法。
13.組成物をネブライザーにおいて噴霧化する、態様1~12のいずれかに記載の方法。
14.ネブライザーが振動メッシュネブライザーである、態様13に記載の方法。
15.エアロゾルが1μm~10μm、好ましくは1μm~7μm、最も好ましくは1μm~5μm、例えばおよそ3μm、3.5μm又は4μmの体積メジアン径を有する、態様1~14のいずれかに記載の方法。
16.エアゾル中の凝集体形成の量が6%以下である(凝集体形成の%はSE-HPLCによって求められるようなものである)、水性担体と、1mg/mL~200mg/mLの濃度で、1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドとを含む組成物を噴霧化することによって得ることができる液滴を含むエアロゾルであって、
該組成物が0.001%~1%の濃度で界面活性剤を更に含み、
該1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが、該組成物中に20mg/mL以上の濃度で存在し、かつ/又は
該組成物を振動メッシュネブライザーにおいて噴霧化する、液滴を含むエアロゾル。
17.エアロゾル中の凝集体形成の量が5%以下、好ましくは4%以下、例えば3%以下、2%以下又は更には1%以下である、態様16に記載のエアロゾル。
18.組成物が、0.001%~1%、好ましくは0.001%~約0.1%、又は約0.01%~約0.1%、例えば約0.001%、0.005%、0.01%、0.02%、0.05%、0.08%若しくは0.1%、好ましくは約0.01%の濃度で界面活性剤を更に含む、態様16又は17に記載のエアロゾル。
19.界面活性剤が非イオン性洗剤から選択される、態様16~18のいずれかに記載のエアロゾル。
20.界面活性剤がポリソルベート(例えばTween 20及びTween 80)及びポロキサマーから選択されるか、又はPEGを界面活性剤様化合物として添加する、態様16~19のいずれかに記載のエアロゾル。
21.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL未満の濃度で存在する、態様18~20のいずれかに記載のエアロゾル。
22.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL以上の濃度で存在する、態様16~20のいずれかに記載のエアロゾル。
23.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL以上の濃度で存在し、かつ該組成物が界面活性剤を含まない、態様16又は17に記載のエアロゾル。
24.ポリペプチドが1つの免疫グロブリン単一可変ドメインを含む、態様16~23のいずれかに記載のエアロゾル。
25.ポリペプチドが2つ以上、例えば2つ又は3つの免疫グロブリン単一可変ドメインを含む、態様16~23のいずれかに記載のエアロゾル。
26.ポリペプチドがRSV又はIL-23に特異的に結合する、態様16~25のいずれかに記載のエアロゾル。
27.ポリペプチドが配列番号1、配列番号2及び配列番号3のうちの1つから選択される態様26に記載のエアロゾル。
28.組成物をネブライザーにおいて噴霧化する、態様16~27のいずれかに記載のエアロゾル。
29.ネブライザーが振動メッシュネブライザーである、態様28に記載のエアロゾル。
30.エアロゾルが1μm~10μm、好ましくは1μm~7μm、最も好ましくは1μm~5μm、例えばおよそ3μm、3.5μm又は4μmの体積メジアン径を有する、態様16~29のいずれかに記載のエアロゾル。
31.凝集体形成の量が6%以下である(凝集体形成の%はSE-HPLCによって求められるようなものである)、免疫グロブリン単一可変ドメインのエアロゾルの調製に好適な組成物であって、水性担体と、1mg/mL~200mg/mLの濃度で、1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドとを含み、
該組成物が0.001%~1%の濃度で界面活性剤を更に含み、かつ/又は
該1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが、該組成物中に20mg/mL以上の濃度で存在する、免疫グロブリン単一可変ドメインのエアロゾルの調製に好適な組成物。
32.凝集体形成の量が5%以下、好ましくは4%以下、例えば3%以下、2%以下又は更には1%以下である、態様31に記載の組成物。
33.0.001%~1%、好ましくは0.001%~約0.1%、又は約0.01%~約0.1%、例えば約0.001%、0.005%、0.01%、0.02%、0.05%、0.08%若しくは0.1%、好ましくは約0.01%の濃度で界面活性剤を含む、態様31又は32に記載の組成物。
34.界面活性剤が非イオン性洗剤から選択される、態様31~33のいずれかに記載の組成物。
35.界面活性剤がポリソルベート(例えばTween 20及びTween 80)及びポロキサマーから選択されるか、又はPEGを界面活性剤様化合物として添加する、態様34に記載の組成物。
36.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL未満の濃度で存在する、態様33~35のいずれかに記載の組成物。
37.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが25mg/ml以上の濃度で存在する、態様31~35のいずれかに記載の組成物。
38.1つ又は複数の免疫グロブリン単一可変ドメインを含むポリペプチドが20mg/mL以上の濃度で存在し、かつ該組成物が界面活性剤を含まない、態様31又は32に記載の組成物。
39.ポリペプチドが1つの免疫グロブリン単一可変ドメインを含む、態様31~38のいずれかに記載の組成物。
40.ポリペプチドが2つ以上、例えば2つ又は3つの免疫グロブリン単一可変ドメインを含む、態様31~38のいずれかに記載の組成物。
41.ポリペプチドがRSV又はIL-23に特異的に結合する、態様31~40のいずれかに記載の組成物。
42.ポリペプチドが配列番号1、配列番号2及び配列番号3のうちの1つから選択される態様41に記載の組成物。
43.組成物中の水性担体が蒸留水、MilliQグレード水又は注射用水(WFI)である、態様1~15のいずれかに記載の方法、態様16~30のいずれかに記載のエアロゾル又は態様31~42のいずれかに記載の組成物。
44.組成物がpH5.5~pH7.5、好ましくはpH7.0に緩衝される、態様1~15のいずれかに記載の方法、態様16~30のいずれかに記載のエアロゾル又は態様31~42のいずれかに記載の組成物。
45.組成物がPBS、リン酸緩衝液、TrisHCl、ヒスチジン緩衝液及びクエン酸緩衝液から選択される緩衝液、好ましくはリン酸緩衝液で緩衝される、態様44に記載の方法、エアロゾル又は組成物。
46.組成物中の緩衝液が10mM~100mM、好ましくは10mM~50mM、例えば10mM又は20mM、特に10mMの濃度を有する、態様45に記載の方法、エアロゾル又は組成物。
47.組成物が等張であるか、又は僅かに低張である、態様1~15のいずれかに記載の方法、態様17~30のいずれかに記載のエアロゾル又は態様31~42のいずれかに記載の組成物。
48.組成物が290±60mOsm/kgのオスモル濃度を有する、態様47に記載の方法、エアロゾル又は組成物。
49.組成物中のオスモル濃度が糖又は塩、好ましくはNaCl、特に130mM NaClの添加によって調整されている、態様47又は48に記載の方法、エアロゾル又は組成物。
50.ポリペプチドを濃縮し、それを選択された緩衝液と交換する工程を少なくとも含む、態様31~42のいずれかに記載の組成物を調製する方法。
51.界面活性剤を0.001%~1%、好ましくは0.001%~約0.1%、又は約0.01%~約0.1%、例えば約0.001%、0.005%、0.01%、0.02%、0.05%、0.08%若しくは0.1%、好ましくは約0.01%の濃度で添加する工程を更に含む、態様50に記載の方法。
52.界面活性剤が非イオン性洗剤から選択される、態様50又は51に記載の方法。
53.界面活性剤がポリソルベート(例えばTween 20及びTween 80)及びポロキサマーから選択されるか、又はPEGを界面活性剤様化合物として添加する、態様52に記載の方法。
54.ポリペプチドを20mg/mL未満の濃度に濃縮する、態様51~53のいずれかに記載の方法。
55.ポリペプチドを20mg/ml以上の濃度に濃縮する、態様50~53のいずれかに記載の方法。
56.ポリペプチドを20mg/mL以上の濃度に濃縮し、かつ界面活性剤を添加しない、態様50に記載の方法。
57.エアロゾル化によってヒト被験体へ送達される薬剤の調製のための態様31~42のいずれかに記載の組成物の使用。
58.噴霧化によってヒト被験体へ送達される薬剤の調製のための、態様57に記載の組成物の使用。
59.振動メッシュネブライザーにおける噴霧化によってヒト被験体へ送達される薬剤の調製のための、態様58に記載の組成物の使用。
60.態様31~42のいずれかに記載の組成物を含有する容器。
61.1つ又は複数の態様60に記載の容器と、エアロゾル送達システムにおける投与のための該組成物の使用説明書とを含むキット。
62.エアロゾル送達システムがネブライザーである、態様61に記載のキット。
63.ネブライザーが振動メッシュネブライザーである、態様62に記載のキット。
64.容器と、該容器に接続されたエアロゾル発生器とを備えるエアロゾル送達システムであって、該容器が態様31~42のいずれかに記載の組成物を含む、エアロゾル送達システム。
65.ネブライザーである、態様64に記載のエアロゾル送達システム。
66.振動メッシュネブライザーである、態様65に記載のネブライザー。
67.治療法に使用される、前述の態様のいずれかに記載の組成物、容器、キット、エアロゾル送達システム又はネブライザー。
68.治療法が呼吸器系疾患の治療である、態様67のに記載の組成物、容器、キット、エアロゾル送達システム又はネブライザー。
69.1つ又は複数の疾患及び/又は障害を予防及び/又は治療する方法であって、態様31~42のいずれかに記載の組成物を、それを必要とする被験体にエアロゾル化によって投与することを含む、1つ又は複数の疾患及び/又は障害を予防及び/又は治療する方法。
70.態様31~42のいずれかに記載の組成物を、それを必要とする被験体にエアロゾル化によって投与することを含む、1つ又は複数の呼吸器系疾患を予防及び/又は治療するための、態様69に記載の方法。
71.呼吸器系疾患がRSV感染症である、態様70に記載の方法。
72.組成物を噴霧化によって投与する、態様69~71のいずれかに記載の方法。
73.組成物を振動メッシュネブライザーによって投与する、態様72に記載の方法。
74.呼吸器系疾患の治療用の薬剤の調製のための前述の態様のいずれかに記載の組成物、容器、キット、エアロゾル送達システム又はネブライザーの使用。
75.呼吸器系疾患がRSV感染症である、態様74に記載の使用。
23IL0075(配列番号1;EVQLLESGGGLVQPGGSLRLSCAASGRIFSLPASGNIFNLLTIAWYRQAPGKGRELVATINSGSRTYYADSVKGRFTISRDNSKKTLYLQMNSLRPEDTAVYYCQTSGSGSPNFWGQGTLVTVSSGGGGSGGGSEVQLVESGGGLVQPGNSLRLSCAASGFTFSSFGMSWVRQAPGKGLEWVSSISGSGSDTLYADSVKGRFTISRDNAKTTLYLQMNSLRPEDTAVYYCTIGGSLSRSSQGTLVTVSSGGGGSGGGSEVQLLESGGGLVQPGGSLRLSCAASGRTLSSYAMGWFRQAPGKGREFVARISQGGTAIYYADSVKGRFTISRDNSKNTLYLQMNSLRPEDTAVYYCAKDPSPYYRGSAYLLSGSYDSWGQGTLVTVSS)が、特許文献16に配列番号2622として記載されている。23IL0075は、重鎖ラマ抗体の3つのヒト化可変ドメイン(IL23 p19の異なるエピトープに結合する119A3v16及び81A12v5、並びにHSAに結合するALB8)からなる。両方のナノボディ中のサブユニットを9G/Sリンカーによって頭尾融合する。
Formulation Buffer:配合物緩衝液
Total Area:総面積
Pre-peaks:プレピーク
Main peak:主ピーク
Post-peak:ポストピーク
REcovery:回収率
Reference:参照
Nebulized:霧化
Histidine:ヒスチジン
Sucrose:スクロース
RSV 420は以下の配列を有する:EVQLVESGGGLVQAGGSLSISCAASGGSLSNYVLGWFRQAPGKEREFVAAINWRGDITIGPPNVEGRFTISRDNAKNTGYLQMNSLAPDDTAVYYCGAGTPLNPGAYIYDWSYDYWGRGTQVTVSSGGGGSGGGGSGGGGSEVQLVESGGGLVQAGGSLSISCAASGGSLSNYVLGWFRQAPGKEREFVAAINWRGDITIGPPNVEGRFTISRDNAKNTGYLQMNSLAPDDTAVYYCGAGTPLNPGAYIYDWSYDYWGRGTQVTVSSGGGGSGGGGSGGGGSEVQLVESGGGLVQAGGSLSISCAASGGSLSNYVLGWFRQAPGKEREFVAAINWRGDITIGPPNVEGRFTISRDNAKNTGYLQMNSLAPDDTAVYYCGAGTPLNPGAYIYDWSYDYWGRGTQVTVSS)(配列番号3)。
表2 種々のネブライザーデバイス及び種々のタンパク質濃度を用いて霧化したRSV420における(SE-HPLCデータからの)オリゴマーの割合
Nebulizer type:ネブライザーのタイプ
Protein conc.:タンパク質濃度
%Oligomer:オリゴマーの%
Jet:ジェット
mesh:メッシュ
表3 種々の緩衝液/賦形剤組成物(緩衝液濃度20mM)中のRSV 434(0.5mg/mL)のDSCによるTmの決定
RSV 434の緩衝液
Melting temperature:融解温度
Citrate:クエン酸塩
acetate:酢酸塩
Na-phosphate:リン酸Na
表4 非霧化材料(REF)と比較した、オムロン株式会社のポケットネブライザーMicroAIR(霧化)による霧化後の種々の配合物緩衝液中5mg/mLのRSV434のSE-HPLC分析データの概要
Ppre-peak:プレピーク
main peak:主ピーク
post-peak:ポストピーク
total recovery:総回収率
total % pre-peak:総プレピークの%
Phosphate:リン酸塩
glycine:グリシン
mannitol:マンニトール
citrate:クエン酸塩
nebulized:霧化
ナノボディRSV434の5mg/ml溶液を、選択された緩働液及び界面活性剤の存在下でオムロン株式会社の手持ち式メッシュネブライザーMicroAirによって霧化した。次いで、霧化前及び霧化後のサンプルをサイズ排除クロマトグラフィーによって分析した。
表5 非霧化(REF)材料と比較した、オムロン株式会社のポケットネブライザーMicroAIR(霧化)による霧化後の種々の配合物緩衝液中5mg/mLのRSV434のSE-HPLC分析データの概要
surfactant:界面活性剤
pre-peak:プレピーク
main peak:主ピーク
post-peak:ポストピーク
total recovery:総回収率
total % pre-peak:総プレピークの%
glycine:グリシンphosphate:リン酸塩
citrate:クエン酸塩
nebulized:霧化
ナノボディRSV434の5mg/ml溶液を、選択された緩働液及び界面活性剤の存在下でメッシュネブライザーAkita Apixneb(Activaero)によって霧化した。次いで、霧化前及び霧化後のサンプルをサイズ排除クロマトグラフィーによって分析した。
ナノボディRSV434の5mg/ml溶液を、選択された緩働液及び界面活性剤の存在下でメッシュネブライザーAkita Apixneb(Activaero)によって霧化した。次いで、霧化前及び霧化後のサンプルをサイズ排除クロマトグラフィーによって分析した。
表6 非霧化材料(REF)と比較した、Akita Apixnebネブライザー(霧化)による霧化後の種々の賦形剤を含むRSV434の5mg/ml溶液のSE-HPLC分析データの概要
surfactant:界面活性剤
pre-peak:プレピーク
main peak:主ピーク
post-peak:ポストピーク
total recovery:総回収率
total % pre-peak:総プレピークの%
glycine:グリシン
phosphate:リン酸塩
citrate:クエン酸塩
nebulized:霧化
ref. no surfactant:参照(界面活性剤なし)
ナノボディRSV434の5mg/ml溶液を、選択された界面活性剤の存在下でジェットネブライザーAkitaJet(Activaero)によって霧化した。次いで、霧化前及び霧化後のサンプルをサイズ排除クロマトグラフィーによって分析した。
表7 非霧化材料(REF)と比較した、AkitaJetネブライザー(霧化)による霧化後の種々の賦形剤を含むRSV434の5mg/ml溶液のSE-HPLC分析データの概要
surfactant:界面活性剤
pre-peak:プレピーク
main peak:主ピーク
total % pre-peak:総プレピークの%
glycine:グリシン
phosphate:リン酸塩
citrate:クエン酸塩
nebulized:霧化
ref. no surfactant:参照(界面活性剤なし)
3つの異なる濃度のナノボディRSV434の溶液を、選択された緩衝液及び界面活性剤としてTween 80の存在下で、メッシュネブライザーAkita Apixneb(Activaero)によって霧化した。次いで、霧化前及び霧化後のサンプルをサイズ排除クロマトグラフィーによって分析した。
3つの異なる濃度のナノボディRSV434の溶液を、選択された緩衝液及び界面活性剤としてTween 80の存在下で、ジェットネブライザーAkitaJet(Activaero)によって霧化した。次いで、霧化前及び霧化後のサンプルをサイズ排除クロマトグラフィーによって分析した。
選択された緩衝液は、0.04%(w:v)Tween80を含む又は含まない10mM NaH2PO4/Na2HPO4(pH7.0)+0.13M NaCl、及び0.04%(w:v)Tween80を含む又は含まないPBS緩衝液であった。PBSの組成は、10.14mM Na2HPO4、1.76mM KH2PO4、2.67mM KCl及び136.9mM NaCl(pH7.8)であった。等張溶液(約290mOsm/kg)を確保するために、NaClの濃度を(先の実験の0.14Mの代わりに)0.13Mに調整した。
更なる霧化実験(三連)を、濃度0、0.02%(w/v)及び0.04%(w/v)の界面活性剤を含む、10mM NaH2PO4/Na2HPO4(pH7.0)+0.13M NaCl中で配合した濃度5mg/mL及び50mg/mLのRSV 434溶液に対して行った。
表9. 50mg/mL及び5mg/mLの濃度でのRSV 434の霧化前及び霧化後の総プレピークの割合(%)及び高分子量(HMW)種の割合(%)(SE-HPLCクロマトグラムの総合データから算出される;図9を参照されたい)(n=3)
total pre-peaks:総プレピークの%
% of HMW species(pre-peak 1):HMW種の%(プレピーク1)
以上の明細書は、当業者が本発明を実施するには十分であるとみなされる。実施例が本発明の一態様の単なる例示を目的とし、他の機能的に同等の実施形態が本発明の範囲内であるため、本発明の範囲は提示の実施例によって限定されない。本明細書中に示され説明されたもの以外の本発明の様々な変更形態は、以上の記載から当業者に明らかとなり、添付の特許請求の範囲の範囲内である。本発明の利点は必ずしも本発明の各々の実施形態によって包含されるわけではない。
meltingtemperature 融解温度
phosphate リン酸
citrate クエン酸
histidine ヒスチジン
図2
pre-peaks プレピーク
phosphate リン酸
citrate クエン酸
glycine グリシン
mannitol マンニトール
図3
pre-peaks プレピーク
phosphate リン酸
citr/phos クエン酸/リン酸
withoutdetergent 洗剤なし
図4
pre-peaks プレピーク
nebulized 霧化
図5
recovery 回収率
図6
Pre-peaks プレピーク
Saline 生理食塩水
図7
Pre-peaks プレピーク
Na Phosphate リン酸Na
図8
Volume MedianDiameter 体積メジアン径
図9
total ofpre-peaks プレピーク合計
HMW species HMW種
min 分
Claims (12)
- 凝集体形成の量が6%以下である(凝集体形成の%はSE-HPLCによって求められる)、2つ以上の免疫グロブリン単一可変ドメインを含むポリペプチドのエアロゾルを調製する方法であって、水性担体と、25mg/mL以上50mg/mL未満の濃度で、2つ以上の免疫グロブリン単一可変ドメインを含むポリペプチドとを含む組成物を噴霧化する工程を含み、
該組成物が、界面活性剤又はポリエチレングリコール(PEG)を含まず、そして
該組成物は、振動メッシュネブライザーにおいて噴霧化する、
エアロゾルを調製する方法。 - 凝集体形成の量が6%以下である(凝集体形成の%はSE-HPLCによって求められる)、免疫グロブリン単一可変ドメインのエアロゾルの調製のための組成物であって、水性担体と、25mg/mL以上50mg/mL未満の濃度で、2つ以上の免疫グロブリン単一可変ドメインを含むポリペプチドとを含み、
該組成物が、界面活性剤又はポリエチレングリコール(PEG)を含まず、そして
組成物が、振動メッシュネブライザーにおいて噴霧化する、免疫グロブリン単一可変ドメインのエアロゾルの調製のための組成物。 - ポリペプチドを濃縮し、それを選択された緩衝液と交換する工程を少なくとも含む、請求項2に記載の組成物を調製する方法。
- エアロゾル化によってヒト被験体へ送達される薬剤の調製のための請求項2に記載の組成物の使用。
- 振動メッシュネブライザーにおける霧化によってヒト被験体へ送達される薬剤の調製のための、請求項4に記載の組成物の使用。
- 請求項2に記載の組成物を含有する容器。
- 1つ又は複数の請求項6に記載の容器と、振動メッシュネブライザーを備えるエアロゾル送達システムにおける投与のための該組成物の使用説明書とを含むキット。
- 容器と、該容器に接続されたエアロゾル発生器とを備えるエアロゾル送達システムであって、該容器が、請求項2に記載の組成物を含み、
エアロゾル発生器が、振動メッシュネブライザーである、エアロゾル送達システム。 - 治療法に使用される、請求項2又は6~8のいずれか一項に記載の組成物、容器、キット又はエアロゾル送達システム。
- 治療法が、呼吸器系疾患の治療である、請求項9に記載の組成物、容器、キット又はエアロゾル送達システム。
- 1つ又は複数の疾患及び/又は障害を予防及び/又は治療するための医薬の調製のための、請求項2に記載の組成物の使用であって、組成物は、それを必要とする被験体に振動メッシュネブライザーにおけるエアロゾル化によって投与される、使用。
- 1つ又は複数の呼吸器系疾患を予防及び/又は治療するための、請求項11に記載の使用。
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